The patent and scientific literature includes various mammalian vector systems such as mammalian virus-based vector systems and mammalian DNA-based vector systems, and how to make and use these vector systems, for instance for cloning of exogenous DNA and expression of proteins, as well as uses for such proteins and uses for products from such proteins.
For instance, recombinant poxvirus (e.g., vaccinia, avipox virus) and exogenous DNA for expression in this viral vector system can be found in U.S. Pat. Nos. 4,603,112, 4,769,330, 5,174,993, 5,505,941, 5,338,683, 5,494,807, 5,503,834, 4,722,848, 5,514,375, U.K. Patent GB 2 269 820 B, WO 92/22641, WO 93/03145, WO 94/16716, PCT/US94/06652, and allowed U.S. application Ser. No. 08/184,009, filed Jan. 19, 1994. See generally Paoletti, “Applications of pox virus vectors to vaccination: An update,” PNAS USA 93:11349–11353, October 1996; Moss, “Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety,” PNAS USA 93:11341–11348, October 1996.
Baculovirus expression systems and exogenous DNA for expression therein, and purification of recombinant proteins therefrom can be found in Richardson, C. D. (Editor), Methods in Molecular Biology 39, “Baculovirus Expression Protocols” (1995 Humana Press Inc.) (see, e.g., Ch.18 for influenza HA expression, Ch.19 for recombinant protein purification techniques), Smith et al., “Production of Huma Beta Interferon in Insect Cells Infected with a Baculovirus Expression Vector,” Molecular and Cellular Biology, December, 1983, Vol. 3, No. 12, p. 2156–2165; Pennock et al., “Strong and Regulated Expression of Escherichia coli B-Galactosidase in Infect Cells with a Baculovirus vector,” Molecular and Cellular Biology March 1984, Vol. 4, No. 3, p. 399–406; EPA 0 370 573 (Skin test and test kit for AIDS, discussing baculovirus expression systems containing portion of HIV-1 env gene, and citing U.S. application Ser. No. 920,197, filed Oct. 16, 1986 and EP Patent publication No. 265785).
U.S. Pat. No. 4,769,331 relates to herpesvirus as a vector. See also Roizman, “The function of herpes simplex virus genes: A primer for genetic engineering of novel vectors,” PNAS USA 93:11307–11312, October 1996; Andreansky et al., “The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors,” PNAS USA 93:11313–11318, October 1996. Epstein-Barr virus vectors are also known. See Robertson et al. “Epstein-Barr virus vectors for gene delivery to B lymphocytes,” PNAS USA 93:11334–11340, October 1996. Further, there are alphavirus-based vector systems. See generally Frolov et al., “Alphavirus-based expression vectors: Strategies and applications,” PNAS USA 93:11371–11377, October 1996.
There are also poliovirus and adenovirus vector systems (see, e.g., Kitson et al., J. Virol. 65, 3068–3075, 1991; Grunhaus et al., 1992, “Adenovirus as cloning vectors,” Seminars in Virology (Vol. 3) p. 237–52, 1993; Ballay et al. EMBO Journal, vol. 4, p. 3861–65; Graham, Tibtech 8, 85–87, April, 1990; Prevec et al., J. Gen Virol. 70, 429–434). See also U.S. application Ser. Nos. 08/675,556 and 08/675,566, filed Jul. 3, 1996 (adenovirus vector system, preferably CAV2) and PCT WO91/11525 (CAV2 modified to contain a promoter-gene sequence within the region from the SmaI site close to the end of the inverted terminal repeat region up to the promoter for the early region 4 (E4)).
There are also DNA vector systems. As to transfecting cells with plasmid DNA for expression therefrom, reference is made to Felgner et al. (1994), J. Biol. Chem. 269, 2550–2561. As to direct injection of plasmid DNA as a simple and effective method of vaccination against a variety of infectious diseases reference is made to Science, 259:1745–49, 1993. See also McClements et al., “Immunization with DNA vaccines encoding glycoprotein D or glycoprotein B, alone or in combination, induces protective immunity in animal models of herpes simplex virus-2 disease,” PNAS USA 93:11414–11420, October 1996.
In 1983, human immunodeficiency virus type 1 (HIV1) was identified as the causative agent of AIDS and was subsequently classified into the lentivirus subfamily of the retrovirus family (Hardy, 1990). Other members of the lentivirus subfamily are equine infectious anemia virus (EIAV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), Simian immunodeficiency virus (SIV) and HIV-2. Much attention within the field of medical virology has been focused on the AIDS pandemic caused by infection with HIV. This lentivirus system has been scrutinized with respect to its molecular biology, immunobiology and pathogenesis in an effort to develop safe and effective vaccines and antiviral therapies. To date, HIV, as well as other lentiviral vaccine studies using different vaccine types have encountered varying degrees of success (Heeney et al., 1994; Daniel et al., 1992; Fultz et al., 1992; Girard et al., 1991; Issel et al., 1992). Further, knowledge is still lacking on the relevance of specific HIV immune responses on vaccine efficacy in humans. Thus, after many years, despite a massive, worldwide effort, an effective HIV1 vaccine is still not available.
Infection of cats with feline immunodeficiency virus (FIV) causes persistent infection and AIDS-like immunosuppressive diseases similar to the HIV infection. As such, FIV infection of cats provides a model for investigating lentivirus immunopathogenicity and vaccine development (Pedersen et al., 1987; Johnson et al., 1994). Similar to HIV, heterogeneity exists, such that multiple FIV subtypes exist (Sadora et al., 1994; Okada et al., 1994). Indeed, like HIV, FIV strains have been classified into four subtypes (A-D) based on genetic differences predominantly in the env and, to a lesser extent gag coding regions.
Thus, while inactivated whole FIV vaccines and inactivated FIV-infected cell vaccines (ICV) have obtained protection against homologous and slightly heterologous FIV (Hosie et al., 1995; Johnson et al., 1994; Yamamoto et al., 1991, 1993), these same vaccines failed to induce protective immunity against distinctly heterologous FIV strains of other subtypes such that induction of protective immunity against a broad range of FIV subtypes may call for a modified or different vaccine approach. This obviously raises concerns relevant to vaccine development. It must also be noted that the FIV prevalence in the cat population is greater than HIV is in man (Verschoor et al., 1996). The development of an FIV vaccine or immunogenic composition is not only useful in providing a model for an HIV vaccine or immunogenic composition but is also therefore of importance from a veterinary health perspective.
More particularly, from the previous FIV studies (Hosie et al., 1995; Johnson et al., 1994; Yamamoto et al., 1991, 1993) it was observed that only cats with significant FIV Env-specific serum reactivity were likely to be protected against homologous challenge exposure. In no case were vaccine-administered animals lacking such a response observed to be protected against FIV challenge (Johnson et al., 1994; Yamamoto et al., 1991, 1993). Together, these results coupled to the observations, to date, that subunit immunogens have not been shown to elicit a protective immune response in target species bring to the forefront several important points relevant to the state-of-the-art for FIV and lentivirus, vaccine development in general. One exception perhaps is with the simian immunodeficiency virus (SIV)/macaque system where certain recombinant subunit preparations (including vaccinia-based recombinants) or combinations of these recombinant subunits have conferred, at least, partial protection from SIV challenge exposure (Hu, 1992; 1994; 1995). This data is somewhat limited in scope since complete protection from infection was not observed and challenge studies were not performed with a distinctly heterologous SIV strain. Moreover, no level of protection was afforded by recombinant subunits devoid of an SIV Env component (Hu et al., 1994).
Relevant to FIV vaccine development, no sub-unit based vaccine candidate has been taught or suggested; there is no teaching as to how to develop a subunit vaccine; and, it is not obvious as to how to develop a subunit-based vaccine candidate.
Secondly, a different or perhaps modified approach, as compared to the inactivated conventional vaccines, needs to be developed to afford protection against heterologous strains (Hosie et al., 1995; Johnson et al., 1994).
Lastly, Env-specific immune responses in protective immunity may be important (Johnson et al., 1994; Yamamoto et al., 1991, 1993). Indeed, in Flynn et al., “ENV-specific CTL Predominate in Cats Protected from Feline Immunodeficiency Virus Infection by Vaccination,” The Journal of Immunology, 1996, 157:3658–3665, at 3664 the authors conclude “that FIV Env-specific CTL may be more effective in protective immunity to FIV infection of domestic cats” such that “future vaccine strategies should be aimed at eliciting both humoral and cell-mediated immune responses that are long-lived, recognize appropriate epitopes on the viral envelope glycoprotein, and are targeted to tissues known to sequester virus.”
It can thus be appreciated that provision of a feline immunodeficiency virus recombinant subunit immunogenic, immunological or vaccine composition which induces an immunological response against feline immunodeficiency virus infections when administered to a host, e.g., a composition having enhanced safety such as NYVAC- or ALVAC-based recombinants containing exogenous DNA coding for an FIV epitope of interest, such as of FIV Env, Gag, or Pol, especially in an immunogenic configuration, or any combination thereof, for instance, FIV Gag-protease, Gag-Pol, or Gag and a portion of Pol (such as a portion of Pol including protease) or all of Env, Gag and Pol or a portion of Pol, in combination, would be a highly desirable advance over the current state of technology. Further, use of such recombinants or compositions containing such recombinants in a prime-boost regimen, e.g., wherein the recombinant composition is used in an initial immunization and a subsequent immunization is with an inactivated FIV, or ICV, or other recombinant subunit preparation would be a highly desirable advance over the current state of technology.
And more generally, it can thus be appreciated that provision of a lentivirus, retrovirus or immunodeficiency virus recombinant subunit immunogenic, immunological or vaccine composition which induces an immunological response against the lentivirus, retrovirus or immunodeficiency virus infections when administered to a host, e.g., a composition having enhanced safety such as NYVAC- or ALVAC-based recombinants containing exogenous DNA coding for a lentivirus, retrovirus, or immunodeficiency virus epitope of interest, such as Env, Gag, or Pol, especially in an immunogenic configuration, or any combination thereof, for instance, Gag-protease, Gag-Pol or Gag and a portion of Pol (such as a portion including protease) all of Env, Gag and Pol or a portion of Pol, in combination such as Env, Gag-protease, in combination, would be a highly desirable advance over the current state of technology. Further, use of such recombinants or compositions containing such recombinants in a prime-boost regimen, e.g., wherein the recombinant composition is used in an initial immunization and a subsequent immunization is with an inactivated lentivirus, retrovirus or immunodeficiency virus, or ICV, or other recombinant subunit preparation, such as a respective inactivated virus, ICV or other recombinant subunit preparation would be a highly desirable advance over the current state of technology (As to “respective”, if the recombinant is, for example an FIV recombinant, inactivated FIV or an FIV ICV preparation may be “respective”).